Dual-Targeting and Multimodal Imaging-Guided Photothermal/Chemodynamic Synergistic Therapy Boosted by Ascorbic Acid-Induced H2O2 in Situ Self-Supply

Tumor-specific targeting and tumor visualization are major obstacles for clinical diagnosis and treatment. Herein, a dual-targeted "all-in-one" nanoplatform (FAA@CM) for trimodal imaging-guided photothermal/chemodynamic synergistic therapy was successfully synthesized by encapsulating Fe₃O₄, Ag₂S, and ascorbic acid with the 4T1 cell membrane. The dual-targeting capability derived from 4T1 cell membrane cloaking and magnetic targeting enables the highly precise tumor-specific delivery of FAA@CM. Fe²⁺ released from FAA@CM in a weakly acidic tumor microenvironment can trigger the Fenton reaction to achieve chemodynamic therapy (CDT). The photothermal performance of FAA@CM not only enables photothermal therapy but also promotes the CDT effect. In order to relieve H₂O₂ deficiency, a biosafe H₂O₂ prodrug, ascorbic acid, was introduced to greatly increase the H₂O₂ concentration in tumors, promoting the Fenton reaction to produce more ^•OH to enhance the oxidative damage to tumors. Interestingly, FAA@CM exhibits trimodal imaging capabilities, including second near-infrared (NIR-II, 1000-1700 nm) fluorescence imaging, photoacoustic imaging, and magnetic resonance imaging, which can guide the laser irradiation, achieving complete elimination of 4T1 tumors in BALB/c mice. This work provided a novel dual-targeted, multifunctional theranostic nanoplatform for highly effective tumor therapy.